The Mechanisms Underlying Helicobacter Pylori-Mediated Protection against Allergic Asthma

Helicobacter pylori, a gram negative pathogen, infects the stomach and gastrointestinal tract and causes pathological damage to these organs. H. pylori infection is more prevalent among people living in developing countries. Allergic asthma is a chronic inflammatory disease of the airways. Hyperinflation, hyperresponsiveness, and abnormal immunological and inflammatory processes in respiratory airways typically occur during an asthma attack. The results of recent studies have suggested an association between H. pylori and asthma risk. However, the role of H. pylori infection in the pathophysiology of asthma is still a matter of debate. The results of some studies indicate an association between H. pylori infection and protection against allergic asthma. Exposure to infectious agents might educate the immune system and provide protection against allergic diseases. H. pylori inflammation also changes gastric hormonal levels and could influence the autonomic nervous system. T-regs could be influenced by the immunological response to H. pylori and then inhibit the Th-2-mediated allergic response. Therefore, H. pylori might play a protective role against asthma. H. pylori can also reduce gastro-esophageal reflux, which is an asthma stimulator. High loads of H. pylori are not always present during infection. It is not definitely clear whether H. pylori is a pathogen or simply an opportunist. It has been suggested that early exposure to H. pylori prevents development of pediatric asthma. Therefore, it is possible that therapeutic products made from H. pylori can be used for the treatment or prevention of asthma.


INTRODUCTION
Helicobacter pylori (H. pylori) is a helically shaped, micro-aerophilic, and gram-negative bacterium that chronically infects the stomach of 45% of the human population. It causes pathologic effects in the stomach and the duodenum. Its presence increases the risk for peptic ulceration, gastric lymphoma, and adenocarcinoma (gastric cancer) (1)(2)(3)(4). H. pylori may also contribute to idiopathic thrombocytopenic purpura and iron and vitamin B12 deficiencies in children. Based on epidemiologic information, people living in developing countries are more likely to acquire H. pylori infection (5)(6)(7).
However, the influence of H. pylori infection on diseases in other organs such as the respiratory system are not fully understood to date. There is some evidence that infection with H. pylori might be associated with the development of bronchiectasis, bronchitis, and lung cancer (7)(8)(9), but it seems that H. pylori infection has no direct role in the development and pathophysiology of bronchial asthma (8)(9)(10). In fact, an inverse relationship between H. pylori infection and the occurrence of allergic asthma has been reported (10)(11)(12).
Allergic asthma is a chronic inflammatory disease of the airways that is characterized by wheezing, coughing, and shortness of breath. Asthma is caused by an exaggerated Th2-mediated immune response to environmental allergens. Allergic asthma is characterized by a Th2 pattern of cytokines and inhibited secretion of IL-12 and IFN-γ (Th1 pattern of cytokines). Type 2 cytokines promote immunoglobulin (Ig) E production and eosinophilic inflammation in the airways (13)(14)(15).
Microorganisms (such as bacteria and viruses) that are responsible for infection in the respiratory system might play complex roles in the development of asthma as stimulatory or inhibitory agents (16,17 The present review will discuss H. pylori infection and its possible connection with allergic asthma. Moreover, potential therapeutic strategies to use H. pylori as a new tool for the prevention and treatment of allergic asthma will also be reviewed.

Microbes and immune system responses
The immune system reacts against different microbes and produces specific responses for the specialized recognition and elimination of different infectious agents (16,22).
Endogenous antigens such as viruses can be eliminated by CD8+ T cells (cytotoxic T lymphocytes) with MHC class I molecules via a cell-mediated cytotoxicity mechanism.
Exogenous microbial antigens such as most bacteria

Allergic asthma
Asthma as a complicated chronic inflammatory airways disease is characterized by mucus hyper-secretion in the epithelium of the airway, showing typical airway hyperresponsiveness in response to allergen stimuli.
Allergic asthma is a common multifactorial disease in childhood but can also develop at any age. Allergic asthma is an important public health problem that reduces the quality of life. Asthma is also associated with high direct

H. pylori-mediated mechanisms against allergic asthma
Previous studies have shown that there is a significant association between H. pylori infection and asthma risk.
Some researchers have suggested that H. pylori infection might be useful to trigger a protective response against allergic asthma (62,66,70). It has been proposed that early exposure to H. pylori is an important mechanism to prevent pediatric asthma development (63,71

Conflict of Interest Statement
There are no conflicts of interest.